Previous work from this laboratory has shown that animals rendered insulin deficient by streptozotocin or alloxan have impaired cell-mediated immunologic responses to T-cell mediated granuloma formation, delayed dermal reactivity, and delayed skin graft rejection. The return to normal of the host response to granuloma formation after insulin therapy suggests that the deficiency in cell-mediated responses may have a reversible metabolic basis. To elucidate the relationships between insulin action and cell-mediated immunity, the model of infection with the facultative intracellular parasite, Listeria monocytogenes, is being utilized. The immune response to Listeria depends upon enhancement of macrophage activation by effector T-lymphocytes. Studies to date suggest: 1) that Listeria proliferate to a much greater extent in diabetic than in control animals; 2) development of dermal hypersensitivity is delayed in diabetic animals; 3) effector T-lymphocyte activity is diminished in diabetic animals. These studies suggest that the defect(s) in insulin deficient animals may be at the level of the effector T-lymphocyte, the macrophage, lymphokine production, or in monocyte and/or macrophage chemotaxis. These studies may provide data suggesting the relationships between insulin action and cell-mediated immunity. They may help elucidate the mechanism(s) for the greater severity of tuberculosis and other cell-mediated infections in poorly treated diabetic patients.